The role of serum factors in the initiation of DNA synthesis in cultured differentiated fetal rat liver cells will be studied as a model for liver regeneration. Serum from partially hepatectomized rats (PH-serum) stimulates DNA and protein synthesis in such liver cell cultures as compared to normal rat serum (NR-serum). Attempts will be made to further purify a high molecular weight serum factor required for the initiation of DNA synthesis in cultured hepatocytes and it will be tested whether the stimulus for DNA synthesis initiation is present in both NR- and PH-sera although in different concentration or whether a new serum factor is present in PH-serum but absent from NR-serum. Growing fetal rat liver cells can reversibly be arrested in GO when arginine is removed from the culture medium in the presence of dialyzed serum. Therefore, the role of serum or serum fractions in stimulating amino acid transport will be studied in growing and resting fetal rat liver cells at different phases of the cell cycle. These studies are aimed at understanding mechanisms by which serum increases the transport of amino acids in fetal rat liver cells and finding out whether limitation of arginine levels inside the cell which lead to the arrest of cell growth in GO is due to reduced arginine transport rates when serum factors have been depleted in the culture medium. The proposed experiments will be helpful to understand the growth control mechanisms in differentiated hepatocytes in culture.